[unreadable] CART was first identified as a mRNA transcript that was upregulated in the rat striatum in response to administration of psychostimulant drugs. CART peptides are widely distributed throughout the central nervous system (CNS) and derive from one of the most abundantly expressed hypothalamic transcripts. Several studies have provided evidence that CART may play a role in the regulation of the HPA axis. However, it is not clear whether CART mediates HPA axis function at the level of the pituitary or if CART regulates activation of the HPA axis through interaction with classic hypothalamic releasing factors. Therefore, characterization of the effects of both central and peripheral administration of CART on the regulation of adrenocorticotropic hormone (ACTH) release will provide key information about the underlying mechanisms of CART's effects on the HPA axis. A second area of interest centers on the putative effects of CART administration on the expression and release of corticotropin-releasing factor (CRF) and vasopressin (AVP) in the hypothalamus. To date there has been little information generated on the subject of a putative CART receptor; therefore, a final aim of this proposal is to isolate and clone a putative receptor for CART. Identification of such a protein will greatly enhance our understanding of the physiological role of CART. The overall goal of our proposed research is to determine the underlying mechanisms of CART regulation of the HPA axis to understand the physiological significance of CART peptides in neuroendocrine centers of the CNS. [unreadable] [unreadable] [unreadable] [unreadable]